ESR Application form

ESR 12: Molecular ecosystem of ERAP four distinct immune cell subsets from patients with ERAP-linked diseases

Recruiting Institution: University Medical Center Utrecht, NL PhD institution: University Medical Center Utrecht, NL	Supervisor: Dr. Jonas Kuiper
Project Description Although ERAPs are genetically associated to a variety of chronic inflammatory conditions, little is known about their transcriptional regulation in immune cells. The UMCU has a unique collection (n~300 samples) of cohorts of transcriptomic data from immune cell subsets, targeted proteomic and genotypes of patients with MHC-I-opathies and autoimmune conditions. The ESR will investigate this OMICs catalogue using bioinformatic and computational data science approaches to reconstruct the transcriptional ERAP ecosystems (i.e. regulator-target analysis and co-expression network analysis) in inflammatory conditions and publicly available data of immune cell subsets to generate testable hypotheses on molecular mechanisms involved in the regulation of ERAPs. These hypotheses will be tested in silico across the available cohort datasets and experimentally in vitro using patient materials and CRISPR-Cas9 based gene editing methods. The presence of modulators of ERAP1 and ERAP2 are explored to predict the impact of therapeutic interference of ERAP in a cell-specific manner and optimize ERAP-targeted therapy for autoimmunity.
Essential Background: Master degree in Biology or Life sciences	Desirable Background: previous experiences (internships) in data science, bioinformatics and/or immunology are a plus.
Local Requirements
Planned Secondments: Academic-Industrial Secondment to HMGU/Metabolon (Munich, GE) 4M, for designing and conducting metabolomic studies for drug toxicity screening.
Planned Starting Date: 1^st Oct. 2021	Application Deadline 31^st May. 2021